食管鳞癌癌变进程中长链非编码RNAuc010etn调控细胞增殖的功能及机制研究

项目名称： 食管鳞癌癌变进程中长链非编码RNAuc010etn调控细胞增殖的功能及机制研究

项目编号： No.81201881

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学2

项目作者： 吕进

作者单位： 南京医科大学

项目金额： 23万元

中文摘要： 长链非编码RNA（LncRNA）在肿瘤的发生发展中具有重要功能。已有诸多研究证实细胞的增殖功能的增强可明显加速癌变进程。追踪文献表明在食管癌变进程中lncRNA对细胞增殖的功能及调控机制的研究尚未见报道。课题组经芯片及qRT-PCR检测发现正常食管粘膜-低级别上皮内瘤变-高级别上皮内瘤变-早期食管癌-中晚期食管癌这一癌变进程中lnc-uc010etn上调均在7倍以上。siRNA干扰uc010etn表达可使细胞增殖能力降低。新近研究证实LncRNA可与miRNA竞争性结合，上调miRNA靶基因表达并执行相关功能。生物信息学分析发现uc010etn存在miR-375结合位点。而已有研究证实食管鳞癌中miR-375表达下调，其靶基因AEG-1/MTDH可明显促进细胞增殖。据此课题组推测uc010etn可与miR-375竞争性结合，解除其对靶基因的抑制，使促增殖蛋白表达上调，加速食管癌变进程。

中文关键词： 长链非编码RNA；PlncRNA-1；SPRY4-IT1；食管鳞癌；

英文摘要： The long noncoding RNA plays an important role in the development and progression of cancer. Mounting evidence have indentified that the enhancement cell proliferation could accelerate carcinogenesis. Tracking the literature suggests that lncRNA study on the mechanism of regulation of proliferation in the process of esophageal carcinoma has not been reported. We detected the tissues of NEE-LIN-HIN-EEC-I/TEC by microarray and qRT-PCR，and found that lnc-uc010etn raised above 7 times in the process of esophageal carcinoma. Recent studies confirmed that the LncRNA could competitively binding with miRNA,then accelerated the expression of miRNA-targeted-gene and executed related functions.The result of MTT assay showed cell proliferation was significantly decreased after disturbance the expression of lnc-uc010etn in KYSE360. Bioinformatics analysis showed that there are two binding sites of miR-375 of lnc-uc010etn. It was identified that miR-375 was downregulated in esophageal squamous cell carcinoma,and its targete gene AEG-1/MTDH was involved in the function of proliferation regulation. Accordingly, we speculated that the The lnc-uc010etn could combine with miR-375 competitively, relieve inhibiting of the targeted gene, then upregulating the expression of proliferation protein and accelerating the process of es

英文关键词： LncRNA；PlncRNA-1；SPRY4-IT1；ESCC；